Incidence of infusion related reactions of daratumumab-hyaluronidase-fihj: Pre-post intervention study of premedication omission.

Abstract

6574 Background: Daratumumab-hyaluronidase-fihj subcutaneous (Dara-SQ) is utilized frequently in the treatment of newly diagnosed and relapsed/refractory multiple myeloma (MM). Initially approved as an intravenous formulation, daratumumab (Dara-IV) showed significant infusion related reactions (IRRs), requiring premedication (acetaminophen, diphenhydramine, dexamethasone, and some add montelukast) prior to each dose. Dara-SQ was shown to be noninferior to Dara-IV with significantly fewer IRRs. Despite the reduced IRR risk, indefinite premedication is also recommended in the package insert for Dara-SQ. Given that IRRs are rare after the first dose of Dara-SQ and premedication extends the time for patients in an infusion center, we investigated whether premedication may be safely omitted after the first cycle. Methods: This pre-post interventional quality improvement study included all patients aged 18 years or older diagnosed with MM or amyloidosis that received at least one dose of Dara-SQ between July 1st, 2020 – December 31st, 2022. Omission of premedication (excluding dexamethasone) after four doses of Dara-SQ was introduced June 1st, 2022. The pre-interventional arm followed standard of care with premedication continued (Arm 1) and post-interventional arm included patients with premedication omitted after fourth dose (Arm 2). Patient demographics, prior therapy, Dara-IV exposure, and premedication usage were collected to evaluate the primary endpoint: incidence of IRR after premedication omission. Secondary analysis included any IRR prior to intervention, timing of reaction, reaction management, and post-reaction management. Results: A total of 102 patients (63 in Arm 1 and 39 in Arm 2) were included in the study, with a median age of 69 (38-86) years old; 52% African American and 54% male. IRR prior to fourth dose occurred in 1.6% (1/63) for Arm 1 vs. 5.1% (2/39) for Arm 2 [ p= 0.6], Dara-IV exposure was 52.4% (33/63) in Arm 1 vs. 10.2% (4/39) in Arm 2 [ p= 0.02], and indication was newly diagnosed MM in 21% (13/63) of Arm 1 vs. 41% (16/39) of Arm 2 [ p= 0.03]. For the primary objective, there were zero reactions in both arms. All three reactions prior to fourth dose occurred after the first dose of Dara-SQ, with a median time to reaction of 4.8 hours. These were all grade 2 per CTCAE v5.0, with all patients discharged home after reaction, and all patients received subsequent Dara-SQ without issues. For the two reactions prior to fourth dose in Arm 2, premedication was omitted after 6 doses in one patient and 8 doses in the other with no further issues on subsequent doses. Estimated therapy time saved was 194 hours, with an estimated savings of $145,500 thus far. Conclusions: IRRs to Dara-SQ occur early, are rare, and mild in course. Omitting premedication after a minimum of four Dara-SQ doses is safe and carries substantial time savings for patients and infusion centers.